17 research outputs found

    Book Review: The Hero Handbook

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    The Hero Handbook, authored by Matt Langdon, offers an informative and practical guide for heroism for both preadolescent readers and adults. The book includes numerous personal anecdotes from his own hero journey and countless references to children’s literature. Each chapter includes “Check Out the Science!” insets written by psychologist Brian Riches, who explains in simple terms the neuroscience underlying various concepts related to heroism. Topics include the hero’s journey, bullying and anti-bullying, the active bystander, and the science of becoming a hero

    Signs Pointing in a New Direction: A Biosemiotic Framework for Biolinguistics

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    Signs Pointing in a New Direction: A Biosemiotic Framework for Biolinguistic

    How Is Meaning Grounded in the Organism?

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    A biosemiotic analysis of Braille

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    Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

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    Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia Âź; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-ÎșB localization and IÎșB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-ÎșB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-ÎșB and degradation of IÎșB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-ÎșB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

    Signs Pointing in a New Direction: A Biosemiotic Framework for Biolinguistics

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    Signs Pointing in a New Direction: A Biosemiotic Framework for Biolinguistic

    Does Inquiry Preempt Representation? A Reply to Teed Rockwell’s “Representation and Radical Empiricism”

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    Winters Andrew M., Stillwaggon-Swan Liz. Does Inquiry Preempt Representation? A Reply to Teed Rockwell’s “Representation and Radical Empiricism”. In: Intellectica. Revue de l'Association pour la Recherche Cognitive, n°60, 2013/2. Pragmatisme(s) et sciences cognitives. pp. 245-250

    How Is Meaning Grounded in the Organism?

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